RESUMEN
BACKGROUND: Interferon gamma release assay (IGRA) is an important method to detect the specific antigen of tuberculosis, which is crucial to the diagnosis of tuberculosis or potential tuberculosis infection. METHODS: We report a case of myelosuppression caused by the use of Melphalan in the treatment of multiple myeloma, resulting in an abnormal decrease in interferon gamma release assay results. RESULTS: We collected blood samples from the patient for retesting and the result of the test did not differ significantly. Upon reviewing the case, it was found that the patient's use of Melphalan treatment resulted in bone marrow suppression and extreme reduction of peripheral blood lymphocytes. Therefore, it is speculated that the abnormal decrease of the interferon gamma release assay result is caused by bone marrow suppression, which is caused by the use of Melphalan. CONCLUSIONS: When patients with multiple myeloma are treated with Melphalan, it can lead to bone marrow suppression and result in false negative interference gamma release assay results. Laboratory staff should consider the existence of such interference and communicate with clinical doctors in a timely manner.
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Ensayos de Liberación de Interferón gamma , Melfalán , Mieloma Múltiple , Humanos , Melfalán/uso terapéutico , Melfalán/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/sangre , Ensayos de Liberación de Interferón gamma/métodos , Masculino , Antineoplásicos Alquilantes/efectos adversos , Persona de Mediana Edad , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Interferón gamma/sangre , Reacciones Falso NegativasRESUMEN
The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.
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Trasplante de Células Madre Hematopoyéticas , Melfalán , Mieloma Múltiple , Insuficiencia Renal , Trasplante Autólogo , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Humanos , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Insuficiencia Renal/terapia , Análisis de Supervivencia , Resultado del Tratamiento , Acondicionamiento Pretrasplante/métodosRESUMEN
We report the successful synthesis of an injectable dendrimer hydrogel (DH) carrying melphalan, a clinical drug for retinoblastoma treatment, in both conjugated and free forms. Polyamidoamine (PAMAM) dendrimer generation 5 (G5) is surface-modified with an acid-sensitive acetal-dibenzocyclooctyne linker and then undergoes azide-alkyne cycloaddition with melphalan-PEG-N3 conjugate to form G5-acetal-melphalan. During the DH gelation between G5-acetal-melphalan and PEG-diacrylate, free melphalan is added, resulting in a hydrogel (G5-acetal-melphalan-DH/melphalan) that carries the drug in both conjugated and free forms. Melphalan is slowly released from G5-acetal-melphalan-DH/melphalan, with the conjugated melphalan released more quickly at pH 5.3 due to acid-triggered acetal bond cleavage. The formulation's in vitro safety and efficacy were established on human corneal epithelia (HCE-2) and retinoblastoma cells (Y79). In an in vivo Y79 tumor xenograft model of retinoblastoma, intratumorally injected G5-melphalan-DH formulation prolonged tumor suppression. This injectable, multimodal, pH-responsive formulation shows promise for intravitreal injection to treat retinoblastoma.
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Dendrímeros , Hidrogeles , Melfalán , Retinoblastoma , Dendrímeros/química , Melfalán/administración & dosificación , Melfalán/química , Melfalán/farmacología , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/patología , Animales , Humanos , Hidrogeles/química , Ratones , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/patología , Línea Celular Tumoral , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacologíaRESUMEN
BACKGROUND: Autologous stem cell transplantation (ASCT) is a pivotal treatment for lymphoma patients. The BeEAM regimen (Bendamustine, Etoposide, Cytarabine, Melphalan) traditionally relies on cryopreservation, whereas the CEM regimen (Carboplatin, Etoposide, Melphalan) has been optimized for short-duration administration without the need for cryopreservation. This study rigorously compares the clinical and safety profiles of the BeEAM and CEM regimens. METHODS: A controlled, randomized clinical trial was conducted with 58 lymphoma patients undergoing ASCT at the International Medical Center (IMC) in Cairo, Egypt. Patients were randomly assigned to either the BeEAM (n = 29) or CEM (n = 29) regimen, with an 18-month follow-up period. Clinical and safety outcomes were meticulously compared, focusing on time to engraftment for neutrophils and platelets, side effects, length of hospitalization, transplant-related mortality (TRM), and survival rates. RESULTS: The findings demonstrate a significant advantage for the CEM regimen. Neutrophil recovery was markedly faster in the CEM group, averaging 8.5 days compared to 14.5 days in the BeEAM group (p < 0.0001). Platelet recovery was similarly expedited, with 11 days in the CEM group versus 23 days in the BeEAM group (p < 0.0001). Hospitalization duration was substantially shorter for CEM patients, averaging 18.5 days compared to 30 days for those on BeEAM (p < 0.0001). Furthermore, overall survival (OS) was significantly higher in the CEM group at 96.55% (95% CI: 84.91-99.44%) compared to 79.31% (95% CI: 63.11-89.75%) in the BeEAM group (p = 0.049). Progression-free survival (PFS) was also notably superior in the CEM group, at 86.21% (95% CI: 86.14-86.28%) versus 62.07% (95% CI: 61.94-62.20%) in the BeEAM group (p = 0.036). CONCLUSION: The CEM regimen might demonstrate superiority over the BeEAM regimen, with faster neutrophil and platelet recovery, reduced hospitalization time, and significantly improved overall and progression-free survival rates. Future studies with longer duration and larger sample sizes are warranted. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under the registration number NCT05813132 ( https://clinicaltrials.gov/ct2/show/NCT05813132 ). (The first submitted registration date: is March 16, 2023).
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Protocolos de Quimioterapia Combinada Antineoplásica , Clorhidrato de Bendamustina , Carboplatino , Citarabina , Etopósido , Trasplante de Células Madre Hematopoyéticas , Linfoma , Melfalán , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Masculino , Citarabina/administración & dosificación , Citarabina/efectos adversos , Citarabina/uso terapéutico , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melfalán/administración & dosificación , Melfalán/efectos adversos , Melfalán/uso terapéutico , Adulto , Linfoma/terapia , Linfoma/mortalidad , Linfoma/tratamiento farmacológico , Persona de Mediana Edad , Acondicionamiento Pretrasplante/métodos , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carboplatino/uso terapéutico , Adulto Joven , Adolescente , Resultado del TratamientoAsunto(s)
Melfalán , Esclerosis Múltiple , Humanos , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/diagnóstico por imagen , Femenino , Adulto , Agonistas Mieloablativos/administración & dosificación , Imagen por Resonancia Magnética , MasculinoRESUMEN
Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m2 fludarabine and 180 mg/m2 Mel or 42 g/m2 treosulfan were used as conditioning.
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Busulfano , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Humanos , Masculino , Femenino , Acondicionamiento Pretrasplante/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Busulfano/uso terapéutico , Busulfano/administración & dosificación , Busulfano/análogos & derivados , Preescolar , Niño , Lactante , Adolescente , Trasplante Homólogo , Melfalán/uso terapéutico , Melfalán/administración & dosificación , Adulto , Errores Innatos del Metabolismo/terapia , Errores Innatos del Metabolismo/mortalidad , Vidarabina/análogos & derivados , Vidarabina/administración & dosificación , Vidarabina/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Adrenoleucodistrofia/terapia , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard treatment for relapsed/refractory lymphoma patients. Yet, the widespread use of BEAM is hindered by carmustine accessibility. This study evaluates the efficacy and safety of PEAM (Cisplatin, Etoposide, Cytarabine, and Melphalan) versus BEAM in auto-HSCT for Hodgkin (HL) and non-Hodgkin lymphoma (NHL) patients. METHODS: We conducted a retrospective single-center study of adult lymphoma patients who received PEAM or BEAM pretransplant conditioning between January 2004 to December 2022, comparing efficacy and safety outcomes. RESULTS: Among 143 patients (median age of 33 years, 58% males), 55 had HL, and 88 had NHL. The overall response rate (ORR) was 86.7% for PEAM and 72.3% for BEAM, and the relapse rate (RR) was lower for PEAM than BEAM (22.9% vs 45.6%). Median time to relapse (TTR) and overall survival (OS) were not reached for either group. PEAM exhibited a shorter time to both neutrophil (NE) and platelet (PE) engraftment compared to BEAM (10 vs 12 days), with a more tolerable gastrointestinal (GI) toxicity profile. CONCLUSIONS: Both BEAM and PEAM showed similar outcomes, demonstrating comparable efficacy in terms of ORR, TTR, and OS for both HL and NHL patients. However, PEAM-conditioning was associated with a shorter time to engraftment and fewer GI adverse events.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carmustina , Cisplatino , Citarabina , Trasplante de Células Madre Hematopoyéticas , Melfalán , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Adulto , Masculino , Femenino , Carmustina/administración & dosificación , Carmustina/uso terapéutico , Estudios Retrospectivos , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/mortalidad , Etopósido/administración & dosificación , Linfoma/terapia , Linfoma/mortalidad , Adolescente , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/mortalidad , Resultado del TratamientoRESUMEN
INTRODUCTION: Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. METHODS: We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. RESULTS: The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. CONCLUSION: The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.
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Protocolos de Quimioterapia Combinada Antineoplásica , Busulfano , Trasplante de Células Madre Hematopoyéticas , Melfalán , Sarcoma de Ewing , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/terapia , Busulfano/administración & dosificación , Busulfano/efectos adversos , Niño , Adolescente , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melfalán/administración & dosificación , Melfalán/efectos adversos , Melfalán/uso terapéutico , Masculino , Femenino , Factores de Edad , Adulto , Etopósido/administración & dosificación , Etopósido/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Vincristina/efectos adversos , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Preescolar , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Resultado del TratamientoRESUMEN
The clinical impact of therapy-related acute leukemias is increasing with the extension of cancer-related survival; however, the origins remain largely unknown. Acute erythroleukemia (AEL), a rare unfavorable type of myeloid neoplasia, may also develop secondary to cytotoxic therapy. The disorder is featured by specific genetic alterations, most importantly multi-allelic mutations of the TP53 gene. While AEL might appear as a part of the therapy-related MDS/AML, spectrum information regarding the genetic complexity and progression is largely missing. We present two AEL cases arising after cytotoxic therapy and melphalan-based myeloablation/autologous peripheral stem cell transplantation due to multiple myeloma (MM). As stated, multiple pathogenic TP53 variants were present unrelated to preexisting MM, in parallel with uninvolved/wild-type hemopoiesis. Potential mechanisms of leukemic transformation are discussed, which include (1) preexisting preneoplastic hemopoietic stem cells (HSC) serving as the common origin for both MM and AEL, (2) the generation and intramedullary survival of p53-deficient post-chemotherapy HSCs, (3) reinoculation of mobilized autologous TP53 mutated HSCs, and (4) melphalan treatment-related late-onset myelodysplasia/leukemia with newly acquired TP53 mutations.
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Leucemia Eritroblástica Aguda , Mieloma Múltiple , Trasplante Autólogo , Mieloma Múltiple/terapia , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Humanos , Persona de Mediana Edad , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/patología , Leucemia Eritroblástica Aguda/terapia , Masculino , Proteína p53 Supresora de Tumor/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Transformación Celular Neoplásica/genética , Mutación , Femenino , Melfalán/uso terapéutico , Melfalán/administración & dosificación , Anciano , Quimioradioterapia/métodos , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/terapia , Neoplasias Primarias Secundarias/genéticaRESUMEN
BACKGROUND: No standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and conflicting evidence. OBJECTIVE: To evaluate efficacy and safety of standard dose (200 mg/m2 = Mel200) versus reduced dose 140 mg/m2 = Mel140) of melphalan in patients with MM undergoing ASCT. DESIGN: A single-center retrospective review of adults with MM for their first ASCT between January 1, 2010, and November 1, 2022, who received Mel200 or Mel140 as conditioning. Primary endpoint was progression-free survival (PFS). Secondary safety and efficacy endpoints included overall survival (OS), incidence of febrile neutropenia and acute kidney injury, and time to engraftment. Subgroup analyses were performed based on patient age and renal function. RESULTS: A total of 322 patients were included in the study, 240 in the Mel200 group and 82 in the Mel140 group. Baseline demographics were similar except patients receiving Mel140 were on average older and had worse kidney function. PFS at 2 years was not different between groups (P = .2335). No difference existed in 2 year PFS or OS for patients < 65 years of age versus ≥ 65 years of age or for patients with CrCl 30-59 mL/min versus CrCl ≥ 60 mL/min within either Mel200 group or Mel140 group (all P > .05). No differences existed between groups across all secondary outcomes. CONCLUSION: Reduced doses melphalan showed no differences in safety or efficacy outcomes versus standard dose even when analyzed based on age and renal function. Larger randomized controlled trials need to be performed to validate these findings.
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Trasplante de Células Madre Hematopoyéticas , Melfalán , Mieloma Múltiple , Trasplante Autólogo , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Mieloma Múltiple/tratamiento farmacológico , Melfalán/uso terapéutico , Melfalán/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo/métodos , Anciano , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto , Resultado del Tratamiento , Acondicionamiento Pretrasplante/métodos , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Alquilantes/administración & dosificaciónRESUMEN
PURPOSE: To evaluate the effectiveness and safety of selective ophthalmic arterial injection (SOAI) for retinoblastoma utilizing a microballoon catheter system with an M chamber. STUDY DESIGN: Retrospective analysis. METHODS AND PATIENTS: This study was sanctioned by theNational Cancer Center Hospital' Independent Ethics Committee. The surgeon was a general interventional radiologist. After confirming that the distal internal carotid artery was not delineated by balloon occlusion and the ophthalmic artery was visualized using digital subtraction angiography, melphalan was manually administered. Notably, in cases presenting bilateral retinoblastoma, both eyes received treatment in a singular, low-dose procedure. Between July 2015 and December 2021, 125 patients with retinoblastoma (68 boys and 57 girls) underwent SOAI at our facility. The average age at initial treatment was 19.3 months. The study covered 250 procedures, with patients undergoing an average of 3.7 procedures. RESULTS: The success rate of the procedure was 99.2%, with a mean procedure duration of 18.3 min. Two distinct technical failures were recorded: one attributed to an internal carotid artery having a wide lumen and the other due to the ophthalmic artery remaining undetected on angiography post-balloon occlusion of the internal carotid artery. Adverse events were minimal but included bronchospasm post-procedure and severe orbital inflammation in 0.8% and 0.4% of cases, respectively. CONCLUSION: SOAI using the microballoon catheter with the M chamber is a feasible and safe procedure for the treatment of retinoblastoma. The success rate was 99.2%. This system can be recommended as intra-arterial chemotherapy for retinoblastoma.
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Inyecciones Intraarteriales , Melfalán , Arteria Oftálmica , Neoplasias de la Retina , Retinoblastoma , Humanos , Retinoblastoma/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/tratamiento farmacológico , Arteria Oftálmica/diagnóstico por imagen , Neoplasias de la Retina/terapia , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/diagnóstico , Estudios Retrospectivos , Femenino , Masculino , Lactante , Preescolar , Melfalán/administración & dosificación , Angiografía de Substracción Digital , Resultado del Tratamiento , Estudios de Seguimiento , Antineoplásicos Alquilantes/administración & dosificación , NiñoRESUMEN
ABSTRACT: Peripheral T-cell lymphomas (PTCLs) have a poor prognosis with current treatments. High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) is used as a consolidation strategy after achieving clinical remission with first-line therapy, as well as in chemotherapy-sensitive relapse if allogeneic transplant is not an option. CD25 is a targetable protein often highly expressed in PTCLs. In this phase 1 clinical trial, we tested the addition of ß-emitting 90yttrium (90Y)-labeled chimeric anti-CD25 basiliximab (aTac) to BEAM (carmustine, etoposide, cytarabine, and melphalan) as conditioning for AHCT for patients with PTCL. Twenty-three AHCT-eligible patients were enrolled, and 20 received therapeutic 90Y-aTac-BEAM AHCT. Radiation doses of 0.4, 0.5, and 0.6 mCi/kg were tested. With no observed dose-limiting toxicities, 0.6 mCi/kg was deemed the recommended phase 2 dose. The most prevalent adverse effect, grade 2 mucositis, was experienced by 80% of patients. As of this report, 6 (30%) of the treated patients had died, 5 due to progressive disease and 1 due to multiple organ failure (median time of death, 17 months [range, 9-21]) after AHCT. Median follow-up was 24 months (range, 9-26) overall and 24 months (range, 13-26) for surviving patients. For patients who received therapeutic 90Y-aTac-BEAM AHCT, the 2-year progression-free and overall survival were 59% (95% confidence interval [CI], 34-77) and 68% (95% CI, 42-84), respectively. 90Y-aTac-BEAM appears to be safe as an AHCT conditioning regimen for PTCL, with no increased toxicity over the toxicities historically seen with BEAM alone in this patient population. This trial was registered at www.ClinicalTrials.gov as #NCT02342782.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carmustina , Citarabina , Etopósido , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Melfalán , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Carmustina/uso terapéutico , Carmustina/administración & dosificación , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/mortalidad , Persona de Mediana Edad , Femenino , Masculino , Melfalán/uso terapéutico , Melfalán/administración & dosificación , Adulto , Acondicionamiento Pretrasplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Citarabina/uso terapéutico , Citarabina/administración & dosificación , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Subunidad alfa del Receptor de Interleucina-2 , Podofilotoxina/uso terapéutico , Podofilotoxina/administración & dosificación , Resultado del TratamientoRESUMEN
Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin protein. MM is the second most common haematological malignancy, with an increasing global incidence. It remains incurable because most patients relapse or become refractory to treatments. MM is a genetically complex disease with high heterogeneity that develops as a multistep process, involving acquisition of genetic alterations in the tumour cells and changes in the bone marrow microenvironment. Symptomatic MM is diagnosed using the International Myeloma Working Group criteria as a bone marrow infiltration of ≥10% clonal plasma cells, and the presence of at least one myeloma-defining event, either standard CRAB features (hypercalcaemia, renal failure, anaemia and/or lytic bone lesions) or biomarkers of imminent organ damage. Younger and fit patients are considered eligible for transplant. They receive an induction, followed by consolidation with high-dose melphalan and autologous haematopoietic cell transplantation, and maintenance therapy. In older adults (ineligible for transplant), the combination of daratumumab, lenalidomide and dexamethasone is the preferred option. If relapse occurs and requires further therapy, the choice of therapy will be based on previous treatment and response and now includes immunotherapies, such as bi-specific monoclonal antibodies and chimeric antigen receptor T cell therapy.
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Mieloma Múltiple , Mieloma Múltiple/terapia , Mieloma Múltiple/fisiopatología , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Humanos , Dexametasona/uso terapéutico , Lenalidomida/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Melfalán/uso terapéutico , Talidomida/uso terapéutico , Talidomida/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Fragilidad , Mieloma Múltiple , Calidad de Vida , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/psicología , Anciano , Masculino , Femenino , Estudios Prospectivos , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melfalán/administración & dosificación , Melfalán/efectos adversos , Melfalán/uso terapéutico , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Prednisona/efectos adversos , Anciano FrágilRESUMEN
For patients with relapsed or refractory AML, sequential conditioning prior to allogeneic stem cell transplantation (alloSCT) is an established and potentially curative treatment option. Early response to treatment during conditioning indicates chemotherapy-responsive disease and may have prognostic value. We retrospectively evaluated blast clearance on day 5 after melphalan, administered 11 days prior to alloSCT as part of a sequential conditioning in 176 patients with active AML. Overall survival (OS) was 52% (95% confidence interval [CI] 45%-60%), and relapse-free survival (RFS) was 47% (95% CI 40%-55%) at 3 years. Patients who achieved early blast clearance did not show a significant improvement in OS and RFS (OS, hazard ratio [HR] HR 0.75, p 0.19; RFS, HR 0.71, p 0.09, respectively), but had a significantly lower non-relapse mortality rate (HR 0.46, p 0.017). HLA-mismatched donor, older age, adverse genetic risk and higher comorbidity scores were associated with inferior survival outcomes. A high initial blast count was only associated with inferior prognosis in patients receiving chemotherapy-only compared to total body irradiation containing conditioning therapy. These results indicate that for patients transplanted with active AML, sensitivity to chemotherapy might be of less importance, compared to other disease- and transplant-related factors.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Trasplante Homólogo , Humanos , Acondicionamiento Pretrasplante/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Masculino , Femenino , Adulto , Anciano , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto Joven , Adolescente , Pronóstico , Melfalán/administración & dosificación , Melfalán/uso terapéuticoAsunto(s)
Antineoplásicos Alquilantes , Melanoma , Melfalán , Neoplasias de la Úvea , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/secundario , Melfalán/administración & dosificación , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/patología , Antineoplásicos Alquilantes/administración & dosificación , Tasa de Supervivencia , Pronóstico , Estudios de Seguimiento , Sistemas de Liberación de Medicamentos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
BACKGROUND: Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. METHODS: Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). RESULTS: The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44-47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. CONCLUSION: Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44).
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Antineoplásicos Alquilantes , Neoplasias Hepáticas , Melanoma , Melfalán , Neoplasias de la Úvea , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/secundario , Melanoma/mortalidad , Melfalán/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/mortalidad , Anciano , Adulto , Tasa de Supervivencia , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Estudios de Seguimiento , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/uso terapéutico , Pronóstico , Anciano de 80 o más Años , Sistemas de Liberación de MedicamentosRESUMEN
SERS (Surface Enhanced Raman Spectroscopy) is a new Raman spectroscopy which relies on Surface Plasmon Resonance (SPR) of metal nanoparticles. We have applied colloidal silver and gold nanoparticles as amplifier agents to enhance nucleotide Raman signals. It is observed that without these enhancing agents, it is impossible to investigate nucleotide spectrum due to weak Raman signals. Interaction mechanism of Melphalan, an anticancer drug with four nucleotides (Adenine, Cytosine, Guanine, Thymine) was investigated using SERS to detect and identify changes due to alkylating process in Raman spectra. After incubating Melphalan drug with nucleotides for 24 h at 37 °C, some changes occurred in SERS spectrum and interpretation of SERS spectra revealed the influence of the alkyl substitution on peaks and Raman shifts. After incubation of Melphalan with each nucleotide, intensity of relevant SERS signals assigned to Amid III group of Cytosine and Amid I of Thymine decreased significantly, confirming alkylating taking place. In this study, we also investigated the effect of nanoparticles type on nucleotide spectrum. We could not obtain useful information in the cases of guanine nucleotide. The SERS spectrum of Cytosine as an example of nucleotides in aqueous solution compared to solid state and results demonstrated that in solid state better signals were obtained than in liquid state.
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Melfalán , Nanopartículas del Metal , Nucleótidos , Espectrometría Raman , Espectrometría Raman/métodos , Melfalán/química , Nucleótidos/química , Nanopartículas del Metal/química , Oro/química , Alquilantes/química , Plata/químicaRESUMEN
PURPOSE: To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). METHODS: Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups. RESULTS: The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804). CONCLUSION: As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.